Our overall objective is to solve the problem of how proteins fold into their native conformations. For this purpose, we are using the methodology of protein chemistry and developing and applying experimental and theoretical techniques to provide an understanding of the internal interactions that stabilize native proteins in aqueous solution. This project is concerned with the theoretical work which involves the use of empirical potentials (including the effects of hydration and entropy) in various computational approaches to study the interactions in protein folding. Emphasis is currently being placed on solving the multiple- minima problem arising from the existence of numerous local minima in the potential energy surface of the protein, the objective being to locate the global minimum on this surface. An understanding of the interactions in proteins is of potential applicability to the elucidation of the role of conformation in biological processes, e.g. the undesirable association of sickle-cell hemoglobin, or the induction of an oncogene product whose properties involve a conformational change when only one amino acid residue in the sequence is changed.